Chronic pressure, grief, and other emotional stresses weaken the body's defenses against cancer and infectious diseases. Together with colleagues at UIC, my laboratory investigates immunosuppressive interactions between the nervous and immune systems wit h an emphasis on the effects of the stress-evoked "sympathetic" catecholamine (CA) neurotransmitters on immune cells. One objective is to understand molecular mechanisms for CA-inhibition of vital proliferative and antitumor activities of thymocytes and T-cells by identifying thymocytic genes regulated by CAs and characterizing the receptors and mechanisms involved. We are testing the hypothesis that mRNA destabilization is an important component of overall immunosuppressive CA gene regulation. A secon d area of study is a novel mechanism by which CAs inhibit the activation and antitumor cytolytic function of natural killer (NK) cells and of cytokine stimulated lymphocytes known as LAK. Pigmented oxidation products in the CA melanin synthetic pathway p rofoundly inhibit NK/LAK, possibly by mechanisms analogous to those for neurotoxic action of dopamine oxidation products in ithe pathogenesis of forms of Parkinson's disease. The physiological antioxidant enzyme superoxide dismutase (SOD) synergizes with macrommolecules produced by LAK cells to protect NK and LAK against inhibition by CA oxidants. We are investigating interactions of the LAK cell product(s) with normal and mutant SOD molecules in search of insights into the neurodegeneration that accomp anies SOD mutation in patients with familial amyotrophic lateral sclerosis.
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